Real-World Outcomes of Immunotherapy in Second- or Later-Line Non-Small Cell Lung Cancer with Actionable Genetic Alterations.

INTRODUCTION: While the efficacy of immune checkpoint inhibitors (ICIs) in treating non-small cell lung cancer (NSCLC) patients with actionable genetic alterations (AGAs) is modest, certain patients demonstrate improved survival. Thus, this study aimed to evaluate the benefits of ICIs in NSCLC patients with diverse AGAs and verify the predictive biomarkers of ICI efficacy. METHODS: From January 2018 to July 2022, this study compared the progression-free survival (PFS) of NSCLC patients with different AGAs treated with ICI monotherapy as second- or later-line therapy at Samsung Medical Center. To ascertain the predictors of ICIs efficacy, we adjusted ICIs' effects on PFS in terms of clinical and molecular biomarkers. RESULTS: EGFR (46.0%) was the most prevalent mutation in 324 patients. In multivariate analysis, PD-L1 positivity (tumor proportion score (TPS) ≥ 1%) (HR = 0.41) and the use of steroids for immune-related adverse events (HR = 0.46) were positive factors for ICI therapy in the AGAs group. Co-existing mutation of STK11 with KRAS mutation (HR = 4.53) and TP53 with MET mutation (HR = 9.78) was negatively associated with survival. CONCLUSIONS: The efficacy of ICI treatment varied across AGA subtypes, but patients with KRAS, MET, and BRAF mutations demonstrated relatively long-duration benefits of ICI therapy. PD-L1 was a significant positive predictive biomarker in all AGA groups.

A Nanoengineered Stainless Steel Surface to Combat Bacterial Attachment and Biofilm Formation.

Nanopatterning and anti-biofilm characterization of self-cleanable surfaces on stainless steel substrates were demonstrated in the current study. Electrochemical etching in diluted aqua regia solution consisting of 3.6% hydrogen chloride and 1.2% nitric acid was conducted at 10 V for 5, 10, and 15 min to fabricate nanoporous structures on the stainless steel. Variations in the etching rates and surface morphologic characteristics were caused by differences in treatment durations; the specimens treated at 10 V for 10 min showed that the nanoscale pores are needed to enhance the self-cleanability. Under static and realistic flow environments, the populations of Escherichia coli O157:H7 and Salmonella Typhimurium on the developed features were significantly reduced by 2.1-3.0 log colony-forming unit (CFU)/cm2 as compared to bare stainless steel (p < 0.05). The successful fabrication of electrochemically etched stainless steel surfaces with Teflon coating could be useful in the food industry and biomedical fields to hinder biofilm formation in order to improve food safety.

Durable omniphobicity of oil-impregnated anodic aluminum oxide nanostructured surfaces.

Recently, various types of porous surfaces have been demonstrated for lubricant (e.g., oil) impregnated omniphobic surfaces. However, the retention of the lubricating liquid within the porous layer and the omniphobic durability still remain challenges. Here, the omniphobic durability of the oil-impregnated surfaces of various types of anodic aluminum oxide (AAO) nanostructures is investigated. The oil impregnation into nanoporous AAO with high porosity enhances droplet mobility by eliminating the pinning site of a contact line on the solid surface, whereas that with low porosity allows the pinning site to result in less mobility. In the cases of nanopillared AAO layers, although the oil-impregnation enhances the repellency to liquids, oil is prone to be depleted by external force such as fluid flow due to the nature of the interconnected oil through the passages between pillars, which limits the omniphobic durability. Among the various types of nanostructured AAO surfaces, the AAO with isolated pore geometry with high porosity exhibits the most durable omniphobicity for a wide range of liquids including organic liquids with low surface tensions. Moreover, the nanoporous AAO surface shows great anti-bacterial adhesion property, reducing the adhesion of bacteria (Escherichia coli K-12) up to 99.2% compared to a bare aluminum surface.

Nanoengineered Superhydrophobic Surfaces of Aluminum with Extremely Low Bacterial Adhesivity.

Bacterial adhesion and biofilm formation on surfaces are troublesome in many industrial processes. Here, nanoporous and nanopillared aluminum surfaces were engineered by anodizing and postetching processes and made hydrophilic (using the inherent oxide layer) or hydrophobic (applying a Teflon coating) with the aim of discouraging bacterial adhesion. Adhesion of Staphylococcus aureus ATCC 12600 (Gram-positive, spherically shaped) and Escherichia coli K-12 (Gram-negative, rod-shaped) was evaluated to the nanoengineered surfaces under both static and flow conditions (fluid shear rate of 37 s-1). Compared to a nonstructured electropolished flat surface, the nanostructured surfaces significantly reduced the number of adhering colony forming units (CFUs) for both species, as measured using agar plating. For the hydrophilic surfaces, this was attributed to a decreased contact area, reducing bacterial adhesion forces on nanoporous and nanopillared surfaces to 4 and 2 nN, respectively, from 8 nN on flat surfaces. Reductions in the numbers of adhering CFUs were more marked on hydrophobic surfaces under flow, amounting to more than 99.9% and 99.4% for S. aureus and E. coli on nanopillared surfaces, respectively. Scanning electron microscopy revealed a few bacteria found on the hydrophobic nanopillared surfaces adhered predominantly to defective or damaged areas, whereas the intact area preserving the original nanopillared morphology was virtually devoid of adhering bacteria. The greater decrease in bacterial adhesion to hydrophobic nanopillared surfaces than to hydrophilic or nanoporous ones is attributed to effective air entrapment in the three-dimensional pillar morphology, rendering them superhydrophobic and slippery, in addition to providing a minimized contact area for bacteria to adhere to.

The extract of Chrysanthemum indicum Linne inhibits EBV LMP1-induced NF-κB activation and the viability of EBV-transformed lymphoblastoid cell lines.

Epstein-Barr virus (EBV) latent infection transforms B lymphocytes into proliferating lymphoblastoid cell lines (LCLs). EBV latent infection membrane protein 1 (LMP1) is required for EBV-mediated B lymphocyte transformation, and LMP1-induced NF-κB activation is essential for LCL survival. To identify a novel inhibitor candidate for LMP1-induced NF-κB activation, crude ethanol extracts of medicinal plants were screened for the potential NF-κB inhibitory activity. Seventy percent ethanol extract of Chrysanthemum indicum Linne extract (CIE) strongly reduced LMP1-induced NF-κB activation. In addition, CIE inhibited LMP1-induced IKKα or IKKß activation. Interestingly, CIE treatment rapidly reduced LCL viability without exhibiting any adverse effects on the viability of human foreskin fibroblasts (HFF), EBV negative Burkitt's lymphoma cell lines (BL41) or HeLa cells. Taken together, CIE has potent inhibitory effect on EBV LMP1-induced NF-κB activation and EBV-transformed LCL viability.